Hemihyperplasia-multiple lipomatosis syndrome

Hemihyperplasia-multiple lipomatosis syndrome (HHML) is a rare overgrowth disorder characterized by asymmetric enlargement of one or more body regions (hemihyperplasia) combined with the development of multiple benign fatty tumors called lipomas throughout the body. The condition is classified among the PIK3CA-related overgrowth spectrum (PROS), as somatic activating mutations in the PIK3CA gene have been identified in affected tissues of many patients. The overgrowth may affect limbs, trunk, or face and can be present at birth or become more apparent during childhood. Lipomas typically develop in subcutaneous tissue and may increase in number and size over time. The syndrome primarily affects the musculoskeletal system, soft tissues, and adipose tissue. Key clinical features include asymmetric body growth (hemihyperplasia), multiple subcutaneous lipomas, and occasionally vascular malformations. Some patients may also exhibit skeletal anomalies such as scoliosis or limb-length discrepancy. The degree of asymmetry and the number of lipomas can vary considerably between individuals. Unlike some other overgrowth syndromes, HHML is generally not associated with significant intellectual disability. There is currently no cure for hemihyperplasia-multiple lipomatosis syndrome. Management is primarily symptomatic and supportive. Surgical intervention may be considered for lipomas that cause discomfort, functional impairment, or cosmetic concerns, and orthopedic management may be needed for significant limb-length discrepancies. As with other hemihyperplasia conditions, monitoring for embryonal tumors (such as Wilms tumor or hepatoblastoma) may be recommended, particularly in childhood, though the exact tumor risk in HHML specifically is not well established. Emerging targeted therapies such as PIK3CA inhibitors (e.g., alpelisib) are being investigated for PIK3CA-related overgrowth conditions and may hold future promise for affected individuals.

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